Brain and Behaviour Laboratory, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Old St Michael's Building, White Swan Road, Portsmouth, PO1 2DT, UK.
Psychopharmacology (Berl). 2022 Jan;239(1):287-296. doi: 10.1007/s00213-021-05990-w. Epub 2021 Oct 15.
Triangulation of approaches (i.e., using several tests of the same construct) can be extremely useful for increasing the robustness of the findings being widely used when working with behavioral testing, especially when using rodents as a translational model. Although zebrafish are widely used in neuropharmacology research due to their high-throughput screening potential for new therapeutic drugs, behavioral test battery effects following pharmacological manipulations are still unknown.
Here, we tested the effects of an anxiety test battery and test time following pharmacological manipulations in zebrafish by using two behavioral tasks: the novel tank diving task (NTT) and the light-dark test (LDT). Fluoxetine and conspecific alarm substance (CAS) were chosen to induce anxiolytic and anxiogenic-like behavior, respectively.
For non-drug-treated animals, no differences were observed for testing order (NTT → LDT or LDT → NTT) and there was a strong correlation between performances on the two behavioral tasks. However, we found that during drug treatment, NTT/LDT responses are affected by the tested order depending on the test time being fluoxetine effects higher at the second behavioral task (6 min later) and CAS effects lower across time.
Overall, our data supports the use of baseline behavior assessment using this anxiety test battery. However, when working with drug exposure, data analysis must carefully consider time-drug-response and data variability across behavioral tasks.
对于使用行为测试的研究，尤其是当使用啮齿动物作为转化模型时，通过对同一结构的几种测试进行三角测量（即使用多个测试），可以极大地提高研究结果的稳健性，这是非常有用的。尽管由于具有高通量筛选新治疗药物的潜力，斑马鱼在神经药理学研究中被广泛使用，但药物处理后行为测试组合的效果仍然未知。
在这里，我们通过使用两种行为任务，即新的水箱潜水任务（NTT）和明暗测试（LDT），测试了药物处理后斑马鱼行为测试组合的效果和测试时间。选择氟西汀和同种警报物质（CAS）分别诱导抗焦虑和类似焦虑的行为。
对于未接受药物治疗的动物，测试顺序（NTT→LDT 或 LDT→NTT）没有差异，并且这两种行为任务之间存在很强的相关性。然而，我们发现，在药物治疗期间，NTT/LDT 的反应会受到测试顺序的影响，具体取决于测试时间，即氟西汀的作用在第二个行为任务（6 分钟后）更高，而 CAS 的作用随时间降低。
总体而言，我们的数据支持使用该焦虑测试组合进行基线行为评估。但是，在进行药物暴露研究时，数据分析必须仔细考虑时间-药物-反应以及跨行为任务的数据分析变异性。
